Whitehead scientists discover heart protein

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Three years ago, a young cardiologist entered the world of basic science to find new ways of helping her most severely ill heart patients. Dr. Jean E. Schaffer was intrigued by what appeared to be a simple question: how does the heart get enough nourishment to meet its tremendous demands for energy, and what happens when those demands are not met? In collaboration with Dr. Harvey F. Lodish at the Whitehead Institute for Biomedical Research, Dr. Schaffer began searching for the transport mechanism that allows heart cells to take up a vital nutrient from body fluids. In the November 4 issue of Cell, Drs. Schaffer and Lodish describe the discovery of the first transport protein for fatty acids in mammalian cells.

"Most tissues in the body use the sugar glucose as their primary energy source, but heart muscle depends more heavily on molecules called long-chain fatty acids," explained Dr. Schaffer, a postdoctoral fellow in the Lodish laboratory. "Changes in the use of long-chain fatty acids relative to other energy sources have been reported in diseases such as cardiac ischemia [leading to angina and heart attack], diabetes and congestive heart failure, but no one knows why these changes occur."

Until now, scientists did not even know how long-chain fatty acids, or LCFAs, got into cells. Some speculated that the LCFAs might simply diffuse through the cell membrane, but Drs. Schaffer and Lodish suspected that normal heart cells must have a mechanism for rapid, controllable uptake of this vital energy source. Using sophisticated gene isolation methods developed at the Whitehead Institute, they began hunting for a gene that directed the synthesis of a specific protein molecule capable of increasing the transport of LCFAs into mammalian cells in tissue culture.

They found a novel protein molecule that is embedded in the cell membrane. It is particularly abundant in heart and fat cells, and does not belong to any previously known family of membrane proteins.

"The discovery of this fatty acid transport protein will allow us to compare energy metabolism in normal and abnormal heart tissue," Dr. Schaffer said. "We should be able to find out why diseased hearts shift away from fatty acid metabolism, and whether this shift exacerbates the disease process."

"Also, some cases of heart disease and sudden death in young children may be associated with genetic defects in the new LCFA transport protein. Knowing the identity of the transport protein will help us diagnose and evaluate the course of disease in these children," Dr. Schaffer added.

Dr. Lodish said, "The extraordinary aspect of this work is that Jean saw a puzzle in clinical practice and was drawn to find the solution herself in basic science. Her discovery is important for basic cell biology as well as cardiology. Jean's research has given us an important new tool for answering vital questions about the way cells take up and utilize important sources of energy."

Dr. Schaffer is supported by an NIH Physician Scientist Award. Support for this project also was provided by MIT's Program of Excellence in Molecular Biology grant from the National Heart Lung and Blood Institute, and a grant from the Massachusetts affiliate of the American Heart Association.